Lacosamide (SPM 927, also referred to as harkoseride or ADD 234037), is chemically (R)-2-acetamido-N-benzyl-3-methoxypropionamide and represented by Formula I. It has been reported to be effective for the treatment of pain, epilepsy, fibromyalgia syndrome, osteoarthritis and migraine. It is also known to be useful for the treatment of CNS disorders in humans.

Lacosamide is available in the United States market as solution and tablet dosage forms with proprietary name of Vimpat®. The tablets are indicated as adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy aged 17 years and older. The solution (injection) dosage form is useful when oral administration is temporarily not feasible.
Lacosamide and its methods of preparation are disclosed in U.S. Reissue Pat. No. 38,551 (hereinafter referred to as the '551 patent). This provides three general methods for the preparation of lacosamide. The first two methods do not involve protection of active groups in intermediate compounds (such as amino, hydroxy and carboxylic acid groups). The third method involves protection of amino group present in D-serine with carbobenzoxy chloride (Cbz-Cl), subsequent O-methylation at hydroxy group followed by benzylamination at carboxylic (—COOH) group and finally removal of the ‘Cbz’ group followed by acetylation produces lacosamide.
An alternative method for the preparation of lacosamide is disclosed in WO 2006/037574 (hereinafter referred to as the '574 application) that comprises O-methylation of N-Boc-protected-D-serine (‘Boc’ refers to t-butoxycarbonyl) directly in one step by avoiding simultaneous formation of methyl ester moiety.
U.S. Publication No. 2009/0143472 (hereinafter referred to as U.S. '472 publication) and IP.com publication (IPCOM000181080D) describes processes for the preparation of lacosamide using trityl or pthalamide protected intermediates, respectively.
General methods known to date for the preparation of lacosamide can be represented by following synthetic scheme (FIG. 1, wherein R is nitrogen protecting group, e.g., Cbz, Boc, trityl, pthalamide etc.).
The inventors of the present invention observed that when protecting the amino group of D-serine, some percentage of hydroxyl groups (of D-serine) were also protected, thereby forming the protected or blocked intermediate compound(s). During the deprotection step (i.e., penultimate stage-FIG. 1), the blocked hydroxyl groups became deprotected and therefore in the last step, (2R)-2-(acetylamino)-3-(benzylamino)-3-oxopropyl acetate [hereinafter, referred as “Impurity-A”] of Formula II is obtained as an impurity along with lacosamide.

The present inventors also observed that commercially available acetic anhydride contained some percentage of propanoic anhydride. As a result, during the last acetylation step (figure I), (2R)-2-propanoylamino-N-benzyl-3-methoxypropionamide of Formula III (hereinafter referred as “Impurity-B”) is obtained as an impurity along with lacosamide.

Therefore, lacosamide produced using known methods contains Impurity-A and/or Impurity-B. Thus, there is a need for simple and cost effective process for the preparation of lacosamide that eliminates or reduces the chances of having said impurities in lacosamide.